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Patients with SARS-CoV-2 infection, exhibit various clinical manifestations and severity including respiratory and enteric involvements. One of the main reasons for death among covid-19 patients is excessive immune responses directed toward cytokine storm with a low chance of recovery. Since the balanced gut microbiota could prepare health benefits by protecting against pathogens and regulating immune homeostasis, dysbiosis or disruption of gut microbiota could promote severe complications including autoimmune disorders; we surveyed the association between the imbalanced gut bacteria and the development of cytokine storm among COVID-19 patients, also the impact of probiotics and bacteriophages on the gut bacteria community to alleviate cytokine storm in COVID-19 patients. In present review, we will scrutinize the mechanism of immunological signaling pathways which may trigger a cytokine storm in SARS-CoV2 infections. Moreover, we are explaining in detail the possible immunological signaling pathway-directing by the gut bacterial community. Consequently, the specific manipulation of gut bacteria by using probiotics and bacteriophages for alleviation of the cytokine storm will be investigated. The tripartite mutualistic cooperation of gut bacteria, probiotics, and phages as a candidate prophylactic or therapeutic approach in SARS-CoV-2 cytokine storm episodes will be discussed at last., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease., Methods: This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance., Results: The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals., Conclusions: Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021., (© 2022. The Author(s).)

Background: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19., Methods: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1., Results: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality., Conclusions: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Most data on the effect of inflammatory bowel disease (IBD) and its treatments on coronavirus disease 2019 (COVID-19) outcomes have not had non-IBD comparators. Hence, we aimed to describe COVID-19 outcomes in IBD compared to non-IBD patients., Methods: We conducted a prospective cohort study of registered IBD patients with confirmed COVID-19 from six provinces in Iran from February to April 2020. Proven COVID-19 patients were followed up at four weeks and the frequency of outcomes was assessed. Multivariable logistic regression was used to assess associations between demographics, clinical characteristics and COVID-19 outcomes., Results: Overall, 2159 IBD patients and 4721 household members were enrolled, with 84 (3.9%) and 49 (1.1%) participants having confirmed COVID-19, respectively. Household spread of COVID-19 was not common in this cohort (1.2%). While hospitalization was significantly more frequent in IBD patients compared with non-IBD household members (27.1% vs. 6.0%, P =0.002), there was no significant difference in the frequency of severe cases. Age and presence of IBD were positively associated with hospitalization in IBD compared with non-IBD household members (OR: 1.06, 95% CI: 1.03-1.10; OR: 5.7, 95% CI: 2.02- 16.07, respectively). Age, presence of new gastrointestinal symptoms, and 5-aminosalicylic acid (5-ASA) use were associated with higher hospitalization rate in IBD patients (OR: 1.13, 95% CI: 1.05-1.23; OR: 6.49, 95% CI: 1.87-22.54; OR: 6.22, 95% CI: 1.90-20.36, respectively). Anti-tumor necrosis factor (TNF) was not associated with more severe outcomes., Conclusion: Age, presence of new gastrointestinal symptoms and use of 5-ASA were associated with increased hospitalization rate among IBD patients, while anti-TNF therapy had no statistical association., (2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: This study was conducted to evaluate the anti-SARS-CoV-2 IgM and IgG antibodies among healthcare workers in Guilan., Methods: This cross-sectional study was conducted on 503 healthcare workers. Between April and May 2020, blood samples were collected from the healthcare workers of Razi Hospital in Rasht, Guilan, Iran. Enzyme-linked immunosorbent assay (ELISA) was used for the detection and quantitation of anti-SARS-CoV-2 IgM/IgG antibodies by using kits made by Pishtaz Teb Company, Tehran, Iran., Results: From a total of 503 participants, the result of the anti-SARS-CoV-2 IgM antibody test was positive in 28 subjects (5.6%) and the anti-SARS-CoV-2 IgG antibody test was positive in171 subjects (34%). Participants in the age group of 35-54 years were significantly more likely to have a positive anti-SARS-CoV-2 antibody test than the age group of 20-34 years (odds ratio = 1.53, 95% CI: 1.04-2.25, P =0.029). Also, physicians were significantly more likely to have a positive antibody test than office workers (odds ratio = 1.92, 95% CI: 1.04-3.54, P =0.037). The wide range of symptoms was significantly associated with the positive anti-SARS-CoV-2 antibody test. The most significant association was observed between fever and a positive anti-SARS-CoV-2 antibody test (odds ratio = 3.03, 95% CI: 2.06-4.44, P < 0.001)., Conclusion: The results of the current study indicated that the seroprevalence of COVID-19 was high among healthcare workers of Guilan Province. It seems that this finding was due to the earlier exposure to COVID-19 and the lack of awareness and preparedness to deal with the pandemic in Iran, compared to other countries., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Heydar Ali Balou et al.)

Background: Rapid increases in cases of COVID-19 were observed in multiple cities in Iran towards the start of the pandemic. However, the true infection rate remains unknown. We aimed to assess the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 18 cities of Iran as an indicator of the infection rate., Methods: In this population-based cross-sectional study, we randomly selected and invited study participants from the general population (from lists of people registered with the Iranian electronic health record system or health-care centres) and a high-risk population of individuals likely to have close social contact with SARS-CoV-2-infected individuals through their occupation (from employee lists provided by relevant agencies or companies, such as supermarket chains) across 18 cities in 17 Iranian provinces. Participants were asked questions on their demographic characteristics, medical history, recent COVID-19-related symptoms, and COVID-19-related exposures. Iran Food and Drug Administration-approved Pishtaz Teb SARS-CoV-2 ELISA kits were used to detect SARS-CoV-2-specific IgG and IgM antibodies in blood samples from participants. Seroprevalence was estimated on the basis of ELISA test results and adjusted for population weighting (by age, sex, and city population size) and test performance (according to our independent validation of sensitivity and specificity)., Findings: From 9181 individuals who were initially contacted between April 17 and June 2, 2020, 243 individuals refused to provide blood samples and 36 did not provide demographic information and were excluded from the analysis. Among the 8902 individuals included in the analysis, 5372 had occupations with a high risk of exposure to SARS-CoV-2 and 3530 were recruited from the general population. The overall population weight-adjusted and test performance-adjusted prevalence of antibody seropositivity in the general population was 17·1% (95% CI 14·6-19·5), implying that 4 265 542 (95% CI 3 659 043-4 887 078) individuals from the 18 cities included were infected by the end of April, 2020. The adjusted seroprevalence of SARS-CoV-2-specific antibodies varied greatly by city, with the highest estimates found in Rasht (72·6% [53·9-92·8]) and Qom (58·5% [37·2-83·9]). The overall population weight-adjusted and test performance-adjusted seroprevalence in the high-risk population was 20·0% (18·5-21·7) and showed little variation between the occupations included., Interpretations: Seroprevalence is likely to be much higher than the reported prevalence of COVID-19 based on confirmed COVID-19 cases in Iran. Despite high seroprevalence in a few cities, a large proportion of the population is still uninfected. The potential shortcomings of current public health policies should therefore be identified to prevent future epidemic waves in Iran., Funding: Iranian Ministry of Health and Medical Education., Translation: For the Farsi translation of the abstract see Supplementary Materials section., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

BACKGROUND: Immunosuppressive agents used in the treatment of inflammatory bowel diseases (IBDs) could potentially increase the risk of coronavirus disease 2019 (COVID-19). We aimed to compare COVID-19 frequency in patients with IBD with their households and identify the related risk factors. METHODS: Firstly, a multi-centered, observational study on 2110 patients with IBD and 2110 age-matched household members was conducted to compare COVID-19 frequency. Secondly, the data of patients with IBD and COVID-19 who had called the COVID-19 hotline were added. Multi variable logistic regression was used to evaluate the effect of age, type and severity of IBD, the number of comorbidities, and medications on the frequency of COVID-19 among the patients with IBD. RESULTS: The prevalence of COVID-19 in patients with IBD and household groups was similar (34 [1.61%] versus 35 [1.65%]; P = 0.995). The prevalence ofCOVID-19 increased from 2.1% to 7.1% in those with three or more comorbidities (P = 0.015) and it was significantly higher in those with severe IBD (P = 0.026). The multivariable analysis only showed a significant association with anti-TNF monotherapy (OR: 2.5, CI: 0.97-6.71, P = 0.05), and other medications were not associated with COVID-19. CONCLUSION: The prevalence of COVID-19 in patients with IBD was similar to the household members. Only patients with IBD receiving anti-TNF monotherapy had a higher risk of COVID-19 susceptibility. This finding could be attributed to the higher exposure to the virus during administration in health care facilities. [ABSTRACT FROM AUTHOR]

The factors affecting the dynamics of lengthening of symptoms and serologic responses are not well known. In order to see how the serologic responses change in relation to the clinical features, we selected a group of 472 adults with a positive IgM/IgG antibody test result from a baseline study of the anti-SARS-CoV-2 seropositivity, assessed their COVID-19 and past medical histories, and followed them up in about 3 months. Nearly one-fourth of the subjects were asymptomatic at the baseline; 12.8% subjects became symptomatic at the follow-up (FU) when 39.8% of the subjects had some persisting symptoms. At the baseline, 6.1% showed anti-SARS-CoV-2 IgM positive, 59.3% only for IgG, and 34.5% for both. At the FU, these figures declined to 0.6, 54.0, and 4.4%, respectively, with the mean IgM and IgG levels declining about 6.3 and 2.5 folds. Blood group A was consistently linked to both sustaining and flipping of the gastrointestinal (GI) and respiratory symptoms. The baseline IgM level was associated with GI symptoms and pre-existing cirrhosis in multivariate models. Both of the baseline and FU IgG levels were strongly associated with age, male, and lung involvement seen in chest computed tomography (CT)-scan. Finally, as compared with antibody decayers, IgM sustainers were found to be more anosmic [mean difference (MD): 11.5%; P = 0.047] with lower body mass index (BMI) (MD: 1.30 kg/m2; P = 0.002), while IgG sustainers were more commonly females (MD: 19.2%; P = 0.042) with shorter diarrhea duration in the FU (MD: 2.8 days; P = 0.027). Our findings indicate how the anti-SARS-CoV-2 serologic response and COVID-19 clinical presentations change in relation to each other and basic characteristics. [ABSTRACT FROM AUTHOR]

Background: The persistence of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) RNA in the body fluids of patients with the novel coronavirus disease 2019 (COVID-19) may increase the potential risk of viral transmission. There is still uncertainty on whether the recommended quarantine duration is sufficient to reduce the risk of transmission. This study aimed to investigate the persistence of SARS-CoV-2 RNA in the nasopharyngeal, blood, urine, and stool samples of patients with COVID-19. Methods: In this hospital-based longitudinal study, 100 confirmed cases of COVID-19 were recruited between March 2020 and August 2020 in Guilan Province, north of Iran. Nasopharyngeal, blood, urine, and stool samples were obtained from each participant at the time of hospital admission, upon discharge, 1 week after discharge, and every 2 weeks until all samples were negative for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) assay. A survival analysis was also performed to identify the duration of viral persistence. Results: The median duration of viral RNA persistence in the nasopharyngeal samples was 8 days from the first positive RT-PCR result upon admission (95% CI 6.91–9.09); the maximum duration of viral shedding was 25 days from admission. Positive blood, urine, and stool RT-PCR results were detected in 24%, 7%, and 6% of the patients, respectively. The median duration of viral persistence in the blood, urine, and stool samples was 7 days (95% CI 6.07–7.93), 6 days (95% CI 4.16–8.41), and 13 days (95% CI 6.96–19.4), respectively. Also, the maximum duration of viral persistence in the blood, urine, and stool samples was 17, 11, and 42 days from admission, respectively. Conclusion: According to the present results, immediately after the hospitalized patients were discharged, no evidence of viral genetic materials was found. Therefore, appropriate treatments were selected for the patients at this hospital. However, we recommend further investigations on a larger sample size in multi-center and prospective randomized controlled trials (RCTs) to evaluate the effects of different drugs on the shedding of the virus through body secretions. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the persistence of SARS-CoV-2 RNA in the nasopharyngeal, blood, urine, and stool samples of patients with COVID-19. Methods: In this hospital-based longitudinal study, 100 confirmed cases of COVID-19 were recruited between March 2020 and August 2020 in Guilan Province, north of Iran. Nasopharyngeal, blood, urine, and stool samples were obtained from each participant at the time of hospital admission, upon discharge, one week after discharge, and every two weeks until all samples were negative for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) assay. A survival analysis was also performed to identify the duration of viral persistence. Results: The median duration of viral RNA persistence in the nasopharyngeal samples was eight days from the first positive RT-PCR result upon admission (95% CI: 6.91- 9.09); the maximum duration of viral shedding was 25 days from admission. Positive blood, urine, and stool RT-PCR results were detected in 24%, 7%, and 6% of the patients, respectively. The median duration of viral persistence in the blood, urine, and stool samples was seven days (95% CI: 6.07-7.93), six days (95% CI: 4.16-8.41), and 13 days (95% CI: 6.96-19.4), respectively. Also, the maximum duration of viral persistence in the blood, urine, and stool samples was 17, 11, and 42 days from admission, respectively. Conclusion: According to the present results, immediately after the hospitalized patients were discharged, no evidence of viral genetic materials was found. Therefore, appropriate treatments were selected for the patients at this hospital. However, we recommend further investigations on a larger sample size in multi-center and prospective randomized controlled trials (RCTs) to evaluate the effects of different drugs on the shedding of the virus through body secretions. [ABSTRACT FROM AUTHOR]